Role of HLA in pregnancy disease/disorders.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"283",leadTitle:null,fullTitle:"Colonoscopy",title:"Colonoscopy",subtitle:null,reviewType:"peer-reviewed",abstract:"To publish a book on colonoscopy suitable for an international medical audience, drawing upon the expertise and talents of many outstanding world-wide clinicians, is a daunting task. New developments in videocolonoscope instruments, procedural technique, patient selection and preparation, and moderate sedation and monitoring are being made and reported daily in both the medical and the lay press. Just as over the last several decades colonoscopy has largely supplanted the use of barium enema x-ray study of the colon, new developments in gastrointestinal imaging such as computerized tomographic colonography and video transmitted capsule study of the colonic lumen and new discoveries in cellular and molecular biology that may facilitate the early detection of colon cancer, colon polyps and other gastrointestinal pathology threaten to relegate the role of screening colonoscopy to the side lines of medical practice. This book draws on the talents of renowned physicians who convey a sense of the history, the present state-of-the art and ongoing confronting issues, and the predicted future of this discipline.",isbn:null,printIsbn:"978-953-307-568-6",pdfIsbn:"978-953-51-6466-1",doi:"10.5772/806",price:139,priceEur:155,priceUsd:179,slug:"colonoscopy",numberOfPages:366,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"1a7ab66798a05a0bc1b4deaa7f1b7492",bookSignature:"Paul Miskovitz",publishedDate:"August 29th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/283.jpg",numberOfDownloads:66553,numberOfWosCitations:20,numberOfCrossrefCitations:14,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:21,numberOfDimensionsCitationsByBook:2,hasAltmetrics:1,numberOfTotalCitations:55,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 2nd 2010",dateEndSecondStepPublish:"November 30th 2010",dateEndThirdStepPublish:"April 6th 2011",dateEndFourthStepPublish:"May 6th 2011",dateEndFifthStepPublish:"July 5th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"53627",title:"Prof.",name:"Paul",middleName:"Frederick",surname:"Miskovitz",slug:"paul-miskovitz",fullName:"Paul Miskovitz",profilePictureURL:"https://mts.intechopen.com/storage/users/53627/images/1772_n.jpg",biography:"Dr. Paul Miskovitz is Clinical Professor of Medicine in the Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College and Attending Physician at the New York—Presbyterian Hospital Weill/Cornell Campus in New York. The author of a variety of articles on gastroenterology, hepatology and internal medicine topics, co-developer of several medical computer software programs, the co-author of three books in the field of gastroenterology, Dr. Miskovitz currently maintains a clinical consultative practice for gastroenterology, hepatology, gastrointestinal endoscopy and gastrointestinal parasitology, and teaches at the Weill Cornell Medical College in New York City and Doha, Qatar. In the Fall of 2009 Dr. Miskovitz was the recipient of a CINE Golden Eagle Award in the Professional Advertising and Promotion Division, Public Service Announcements, for participation in the CBS Cares Colonoscopy Sweepstakes, a very successful PSA designed to increased public awareness nationwide with regard to colorectal cancer screening using colonoscopy.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Weill Cornell Medicine",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1020",title:"Colorectal Surgery",slug:"gastroenterology-colorectal-surgery"}],chapters:[{id:"21216",title:"Introduction - A Brief Overview of Selected Aspects of Colonoscopy: Past, Present and Future",doi:"10.5772/10677",slug:"introduction-a-brief-overview-of-selected-aspects-of-colonoscopy-past-present-and-future",totalDownloads:2353,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Paul Miskovitz",downloadPdfUrl:"/chapter/pdf-download/21216",previewPdfUrl:"/chapter/pdf-preview/21216",authors:[null],corrections:null},{id:"18745",title:"Preparing for Colonoscopy",doi:"10.5772/20843",slug:"preparing-for-colonoscopy",totalDownloads:10615,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Rosalinda S. 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Mammalian pregnancy with haemochorial placentation is an immunological contradiction with suppression of an immune response against the semi allogeneic foetus having inherited paternal antigens foreign to mother [1]. The foetus is not rejected as it would have, ideally in case of an unmatched organ transplant, wherein the immune system forbids the incursion of any genetic material or protein foreign to itself [2].
The protective mechanism which leads to acceptance of the semi allogeneic foetus includes: (i) Complete separation of maternal and foetal blood circulation. (ii) Low expression of foetal antigens that may stimulate graft rejection. The trophoblast cells originating from foetus lack expression of classical HLA class Ia and class II antigen except for very low expression of HLA-C antigens. They express HLA class Ib antigens which are known to modulate immune responses at the feto-maternal interface [3]. (iii) Involvement of both mother and foetus in order to maintain pregnant uterus as an immune privileged site. (iv) Programming of the maternal immune response by factors obtained from placental and extra placental membrane [4].
Maternal and foetal cells interact in co-ordination to maintain an immune privileged environment at feto-maternal interface; some instances do occur which lead to maternal sensitization thereby leading to various disorders in the foetus/neonate. Alloimmunization during pregnancy is the stimulation of maternal immune response by the paternal inherited foetal or placental antigens [5].
The recognition of antigens as self and non-self is the essential process by which the immune system determines whether or not to develop an immune response. The response of the maternal immune system will depend on genetic and acquired factors related to the foetus and to antigen immunogenicity. Maternal alloimmunization occurs when the foetal and the maternal lymph combine due to rupture of placental barrier which often happens during delivery, although feto-maternal haemorrhage (FMH) may also result early in pregnancy. The instance of FMH has been observed in 7, 16, and 29% of mothers during their first, second and third trimesters, respectively [6]. Other maternal factors responsible for maternal sensitization involve factors such as Rh incompatibility, major surgical procedure, blood transfusion, multiparity, or operative removal of placenta [7].
The major antigens against which the maternal alloimmunization occurs are RBC, granulocytes (neutrophils), human platelet antigens and HLA antigens. The sensitization against these antigens leads to disorders, such as, haemolytic disease of foetus and newborn (HDFN), neonatal alloimmune neutropenia (NAN) and foetal and neonatal alloimmune thrombocytopenia (FNAIT), respectively.
Till now most of the studies have addressed the maternal alloimmunization relating to Rh and platelet antigen, this book chapter aims at exploring the role of human leukocyte antigen (HLA) in pregnancy and alloimmunization along with other factors.
The human leukocyte antigen (HLA) also known as the major histocompatibility complex (MHC) play a very crucial role in enabling the immune system to differentiate between “self” and “non-self-antigen” [8]. It is situated on the short arm of human chromosome 6p21.3, and codes for nearly 130 structural genes known to function in antigen presentation to immune system thereby modulating the immune response. It is categorized into three classes i.e., class I, class II and class III [9]. The HLA class I gene is further classified into classical HLA class Ia genes (HLA-A, -B, -C) and non-classical HLA class Ib genes (HLA-E, -F, -G) [3]. The non-classical HLA class Ib genes show limited polymorphism as compared to those of classical HLA class Ia genes [10]. The HLA class II is differentiated into HLA-DR,-DQ ,-DM and -DP.
The HLA class I molecules are known to interact with CD8+ T cells, natural killer cells (NK cells), and class II molecules with CD4+ T cells, respectively [11, 12] to elicit an immune response in order to eliminate the foreign or non-self-antigens. In contrast the non-classical HLA class Ib molecules interact with natural killer cells (NK cells) and other immune cell to develop an immunological tolerogenic effect. HLA plays a very important role in transplantation, as it is known to evoke an immune response to the transplanted graft, thus are very critical in pregnancy from gamete formation to completion of development, as foetus is the most successful semi-allograft.
The non-classical HLA class Ib molecules, primarily HLA-G plays a very important role in maintaining maternal tolerance i.e., an immunosuppressive state during pregnancy thereby contributing to foetal endurance and growth. Consequently inability in maintaining the maternal tolerance to the foetus, adversely affects the pregnancy leading to complications such as recurrent spontaneous abortion, foetal growth restriction, and preeclampsia [13]. Also HLA-C along with KIR (killer-immunoglobulin receptor) has been implicated to play a role in placentation. Thus, the role of HLA along with other immune cells may be implicated in maintaining pregnancy as well as at time in leading to pregnancy complications.
Among the non-classical HLA class Ib genes HLA-G is the most studied because of its role in immune modulation during pregnancy and its association with complexities like pre-eclampsia and recurrent spontaneous abortion in pregnancy [14].
The non-classical class Ib HLA-G gene is situated near to the classical class Ia HLA-A gene on chromosome 6 and is also greatly homologous to it. The HLA-G gene comprises of seven intronic regions and eight exonic regions. The exon 1 codes for the signal peptide. The exons 2–4 code for the external part of HLA-G molecule which consist of three parts viz. α1, α2 and α3 domains, exon 5 encodes for the transmembrane region, where as exon 6 and a very short part of exon 8 encode for the cytoplasmic tail of the HLA-G molecule. The HLA-G gene is translated into a 38 kDa protein having similar structure as that of HLA class I antigens. It consists of a heavy chain that binds a light chain β2-microglobulin a protein coded by a gene on chromosome 15. The α1 and α2 extracellular domain of heavy chain form the peptide binding groove [15].
The HLA-G antigen has seven splice variants (HLA-G1-HLA-G7) as a result of alternative splicing event of the mRNA from the single HLA-G gene, of which HLA-G1 is the full length variant and the rest are formed by out-splicing of exons. Out of the seven isoform HLA-G1, HLA-G2, HLA- G3 and HLA-G4 are membrane-bound and the remaining three i.e., sHLA-G5, sHLA-G6 and sHLA-G7 are soluble isoforms [16]. The coding region of HLA-G gene shows meagre polymorphism but the polymorphisms that are present are equally shared by introns and exon 2, 3 and 4. Most of these polymorphism do not modify the protein sequence and those which do modify the protein sequence permit to be grouped in major allele groups like G*01::xx, G*01:02, G*01:03: xx, G*01:04: xx, G*01:05 N (null allele), G*01:06, and G*01:07 to G*01:18. Overall there are 61 alleles and 19 protein groups representing an amino acid substitution have been delineated in the HLA-G gene sequence [WHO Nomenclature Committee for factors of the HLA System and the International Immunogenetics Information System (IMGT)/HLA Database] [15].
HLA-G expression was first reported on human non-villous cytotrophoblast cells [17]. Its expression is stringently confined to certain cells, being largely expressed in extravillous cytotrophoblast cells. HLA-G5 a soluble variant is present throughout the placenta, within the chorion membrane, maternal blood and the decidua [18]. Apart from placental expression soluble HLA-G proteins are present in peripheral blood of pregnant women, non-pregnant women and men. The presence of sHLA-G in the blood of non-pregnant women indicates that it may play an important role in reproduction even before conception. Soluble HLA-G is also found in follicular fluid, fertilized oocyte and in male reproductive tissue including semen [14]. HLA-G presence can also be detected in tissues like thymic medulla, cornea, pancreas and in human mononuclear phagocytic cells [53]. Its expression can be stimulated in condition following transplant, viral infections, autoimmune diseases and tumors [19].
Both coding and non-coding regions of HLA-G gene display polymorphism. Exonic polymorphism may affect biological function such as binding of peptides or production of isoforms; whereas intronic polymorphism may influence the expression of the gene. Codon 31, 35, 57 and 69 of Exon 2 and codon 93, 107 and 110 of exon 3 coding region display majority of the polymorphism. A large number of SNPs (single nucleotide polymorphism) have been found in the non-coding region, including the promoter region at 5′UTR (untranslated region) and the 3′UTR. Some of these polymorphisms located near the regulatory element have an impact on the binding of the corresponding factors.
A 14 bp deletion/insertion have also been reported in the 3′UTR region of exon 8. These 14 bp del/ins are suspected to affect the size and stability of the mRNA transcripts. It was noticed by Rousseau et al. that a 14 bp insertion of sequence (5′-ATTTGTTCATGCCT-3′) lead to deletion of 92 bp sequence in the 3′UTR region, thereby resulting in production of more stable transcript. Few polymorphisms that may also effect the stability of mRNA transcripts, including the SNPs located at the position +3142 (C/G) and at +3172 position (G/A) in the 3′UTR region [19].
Approximately 40% of the decidual tissue comprise of maternal immune cells at the beginning of pregnancy. Majority of these immune cells are natural killer (CD56 bright 16−) cells which are distinct from the NK cells (CD56 dim16+) present in the peripheral blood as the decidual NK cells have reduced cytotoxic activity. Also the decidual NK cells have a higher expression for genes encoding for integrins, lectin-like receptors, KIR (killer-immunoglobulin like receptors) and cytokines. Along with the presence of NK cell decidual tissue also show the presences of macrophages, T lymphocytes and dendritic cell [19, 20].
The trophoblast cells of the embryo express HLA-G antigen since the beginning of the first trimester and are present till the end of pregnancy. The interaction of HLA-G protein at the feto-maternal interface with the immune cell of the decidua ensures the foetal tolerance by inhibition of cytotoxic activity of NK cells and CD8+ T cells, suppressing the proliferation of alloreactive CD4+ T cells, suppressing the B cell activity, leading to the secretion of Th2 cytokines and stimulation of regulatory T cells (Treg) [19].
HLA-G intercedes its immunosuppressive activity by interaction of alpha 1 domain with inhibitory receptors expressed on immune cells. Leukocytes express inhibitory receptors like immunoglobulin-like transcripts (ILT)-2, ILT-4 and KIR. CD4+ and CD8+ T cells, B cells, monocytes, macrophages and myeloid dendritic cells (DC) display ILT-2, interact with only heterodimers of HLA-G1 or sHLA-G5 and ß2m. ILT-4 displayed by monocytes, macrophages and myeloid DC’s have the capability to also interact with monomers of HLA-G whereas the NK cells interact through the KIR2DL4 expressed by them [19] (Figure 1). The interaction of these immune cells like decidual NK cells, CD4+ and CD8+ T cells which are HLA-G negative cells with trophoblast cell expressing HLA-G molecule leads to the acquisition of HLA-G molecule by immune cells thereby making them HLA-G+ cells through a process called as trogocytosis. Trogocytosis is a mechanism by which surface molecules may be transferred from one cell to another via cell to cell contact. The acquisition of the HLA-G molecule by these immune cells contributes to an immune suppressive milieu without them expressing HLA-G molecule, but only temporarily displaying it [21]. The acquiring of the HLA-G molecule by the decidual NK cells is preceded by a cycle of internalization, degradation and reacquisition of HLA-G. This cycle helps NK cells to maintain both tolerance and immune function [20].
HLA-G molecules expressed by the trophoblast cells interact with the inhibitory receptor KIR2DL4 expressed by the NK cells, ILT-2 (Ig-like transcript 2) expressed by NK cells, CD4+ and CD8+ T-cells and B-cells, and ILT-2 and ILT-4 expressed by macrophages and dendritic cells. The interaction of the HLA-G with its cognate receptors leads to immune tolerogenic effect thereby leading to the acceptance of the foetus by the maternal immune system.
Abnormal placentation and immunological interaction at the feto-maternal interface are believed to play very crucial role in placenta-mediated complication of late pregnancy (viz. pre-eclampsia, foetal growth restriction, still birth and placental abruption) and foetal rejection in some pathological pregnancy, respectively. Deficient level of HLA-G expression and polymorphisms at HLA-G loci are known to be correlated to pregnancy complication especially pre-eclampsia and recurrent miscarriages (RM).
Pre-eclampsia is a pregnancy disorder which is clinically evident in the late second and third trimester of pregnancy [19]. It is characterised by high blood pressure, proteinuria and oedema associated with organ damage and prematurity. It is known to be a major cause of perinatal deaths, premature births and intrauterine growth restriction with an occurrence of 5–10% of all the pregnancy [22]. Though the major cause is unknown, various studies suggest that it may be related to maladapted immune system, with low levels of immune regulatory cell and low expression of HLA-G molecules [23]. The development of pregnancy has been strongly associated with level of soluble HLA-G molecules in the maternal blood. Maternal serum with higher levels of sHLA-G has been identified in females with successful pregnancy when compared with pre-eclampsia patients [24]. Lower sHLA-G levels in the maternal blood, with down regulated HLA-G and decreased proportion of HLA-G+ cells have been identified in patients with preeclampsia and are thought to be are strongly associated with preeclampsia [24, 25, 26]. The 14 bp ins/del in the 3′UTR of region exon 8 have been extensively studied, and it has been reported to be related to severe pre-eclampsia [15]. But on the contrary, there are studies which have reported no significant association of the 14 bp polymorphism with preeclampsia [24, 25, 26] implicating that differences in the ethnic population should be considered for the association between HLA-G 14 bp polymorphism and serum sHLA-G level. The SNP at position +3172 (G/A) leading to decreased in mRNA stability has been linked to pre-eclampsia [19]. Steinborn et al. reported that women with soluble HLA-G levels lower than 9.95 ng/ml have a risk of 7.1 for developing placental abruption during pregnancy as compared to healthy women [3].
Recurrent spontaneous abortion (RSA) is defined as the loss of two or more consecutive pregnancy with the same partner [27]. The major causes of RSA are considered to be chromosomal abnormalities, anatomical anomalies and endocrine disorders along with immunologic dysfunction [28]. Many studies have reported increased occurrence of HLA-G allele homozygous for 14 bp ins in women with RSA [19]. Also, a study has reported that decreased expression of HLA-G suppresses the function of decidual NK cells and thereby may lead to RSA [28]. SNPs−1573T>C and −1746C>A in the promoter region of HLA-G gene are shown to be associated with RSA [29]. As the level of sHLA-G is known to be associated with the pregnancy complication, the measurement of sHLA-G protein may be useful in primary diagnosis for the pathogenesis of pregnancy complications.
Health of a foetus during pregnancy depends on the supply of nutrients and oxygen to the placenta. During placentation the foetal trophoblast cells infiltrate into the uterine wall, transforming the spiral artery (maternal artery supplying blood to the placenta) into a high-conductance vessel, thereby increasing the blood flow to about 100 folds [30]. This transformation allows adequate time for gas exchange and also provides sufficient nourishment to the foetus. Defective infiltration of the trophoblast cells into the uterus leads to failure in arterial conversion, thereby leading the arterial blood to squirt into the intervillous space from the non-transformed arteries causing impairment of the villous tree (placentation). The impaired placentation leads to reduced transport of oxygen and starving of the foetus. The clinical manifestation of this failure may result in disorders such foetal growth restriction (FGR), preeclampsia, recurrent miscarriage (RM), unexplained still birth, placental abruption and preterm labour [31, 32].
The uterus shows abundance of decidual natural killer cells (NK cells) and thus, is thought to be involved in placentation and thereby in foetal development. Placenta is the site at which maternal allorecognition of the foetus takes place, wherein the foetal extra villous trophoblast cells (EVTs) encroach and unify with the maternal immune cells. Interaction of maternal KIR present on the uterine NK cells and its corresponding ligand, HLA-C which is the only classical HLA class I antigen expressed on the trophoblast cells of the foetus are claimed to regulate the process of placentation.
There are approximately 14 different KIR genes existing in a linear array in the leukocyte receptor complex (LRC) on chromosome 19q13.4. KIRs are differentiated on the basis of number of extracellular Ig-like domain (2 or 3) and cytoplasmic tail (long or short). They are known to regulate the activity of NK cells, either conferring them with an inhibitory or activating signal. Interaction of KIR with a long cytoplasmic tail (e.g., KIR2DL1) with its corresponding ligands leads to generation of an inhibitory signal, where as those having a short tail (e.g., KIR2DS1) results in activation of NK cells.
The activating and inhibitory genes are differentiated into two haplotype A and B. The KIR A haplotype is the most frequently occurring haplotype and consists of six inhibitory genes. The KIR B haplotype consist of gene which are more variable in their genetic content and are mostly activating KIR. Hence an individual’s KIR genotype can be designated as “AA”, “AB”, and “BB”.
The most important ligand for KIR is the HLA-C molecules, and there are approximately 4000 alleles of HLA-C. The HLA-C are differentiated into two distinct group by KIR, i.e., HLA-C1 and HLA-C2 [33]. HLA-C molecules with amino acid asparagine (Asn) at position 80 belong to HLA-C1 group, where as those with amino acid lysine (Lys) at the 80th position belong to group C2 of HLA-C. KIR2DL2/3 (inhibitory receptor) interacts with HLA-C1 allotype and KIR2DL1 and KIR2DS1 act as receptors for HLA-C present in C2 group [34].
Existence of KIR B haplotype in mother confers protection from pregnancy complications, where as its absence may increase the risk of complications [35]. The KIR B haplotype consist of activating KIR2DS1 receptor, which on interacting with its cognate ligand induces the NK cells to secrete granulocyte-macrophage colony stimulating factors and other chemokines known to promote placental trophoblast invasion. It also consists of KIR2DL1*004 which is the most common inhibitory KIR2DL1 allele on the B haplotype, and is known to have a weak interaction with HLA-C2 allotype as compared to alleles present on KIR A haplotype [36]. On the contrary, mothers homozygous for KIR A haplotypes (KIR “AA” genotype), with foetus having an additional C2 copy as compared to mother (i.e., mother C1/C2 with foetus C1/C2 or mother C1/C2 with foetus C2/C2), that to when the extra copy is of paternal origin are at an increased risk of having a complicated pregnancy [6]. As mothers with KIR AA haplotype have two copies of inherited inhibitory KIR for HLA-C2 allotype i.e., KIR2DL1, thus when the mothers uterine NK cells possessing KIR AA genotype interact with foetal trophoblast cells expressing HLA-C2 allotype, it induces a strong inhibitory effect on NK cell which is one of the reasons for defective placentation and in turn for various pregnancy related complications [37] (Figure 2).
Model for maternal KIR/foetal HLA-C interaction at the placentation site. The figure depicts foetus homozygous for HLA-C2 group with one paternally inherited HLA-C2 molecule. If the mother possesses KIR AA genotype, then the inhibitory KIR2DL1 receptor will interact with HLA-C2 molecule expressed by trophoblast cells leading to strong inhibition of uterine NK cells thereby resulting in defective placentation. On the contrary if the mother possess KIR AB or BB genotype, the activating KIR2DS1 receptor present in the KIR B haplotype interacts with HLA-C2 molecule expressed by trophoblast cells stimulating the of uterine NK to produce cytokines such as GM-CSF thereby resulting in normal placentation.
H-Y antigens are a class of minor histocompatibility antigens (mHAs), encoded on Y-chromosome are omnipresent in male cells including foetal and trophoblast cells. H-Y antigens exhibit a large amount of similarity to H-X antigen encoded on the X-chromosome, but they possess few distinct regions which make them highly immunogenic in nature. The H-Y alloimmunity has turned out to be, one of the potential reasons for SRM during pregnancy.
SRM is defined as three or more consecutive miscarriages following a successful pregnancy as compared to primary recurrent miscarriage (PRM), which is characterized by three or more miscarriages without a previous successful birth. PRM is supposed to be caused because of chromosomal defect along with improper implantation of the embryo, whereas SRM are more probably caused due to immunological responses [38].
Generally, during pregnancy the cellular and humoral anti-HY immune response is well tolerated by the foetus, but in minority of cases the H-Y alloimmune response may lead to complications during early or late pregnancy. It has been implicated that pregnancy with a male foetus results in the development of alloimmune response towards the H-Y antigen by mother’s immune system, thereby predisposing the mother to SRM and also impacting the prospect of subsequent pregnancy negatively in terms of perinatal complications and live birth [38, 39].
The presence of H-Y restricted HLA alleles along with H-Y antibodies, have also been related to the development of SRM and other pregnancy complications [38, 40]. The term “H-Y restricting HLA” is utilized to describe HLA alleles documented till date, which functionally exhibit H-Y peptides. H-Y restricting HLA alleles include the following HLA class I alleles: HLA-A*01, HLAA*02, HLA-B*07, HLA-B*08, HLA-B*52, HLA-B*60 and HLA class II alleles: HLA-DRB1*15, -DQB1* 0501/2, -DRB3*03.
Possessing a HY restricting HLA class II alleles substantially decreases the prospect of live birth in patients with SRM and firstborn boys as compared to those with firstborn girl. It is implicated that the prospect of live birth decreases in a dose-response fashion with increasing number of maternal HY-restricting HLA class II alleles in patients with firstborn boys [40]. Maternal possession of HY restricting HLA class II alleles also reduces the long-term chance of live birth in females with SRM [41]. Whereas a mother homozygous for HLA-G 14 bps ins and carrying HY restricting class II alleles are predisposed to SRM with the first born boy and also negatively affect the birth weight of the boy [42].
In a study, antibodies against both HLA and H-Y antigens during early pregnancy were significantly higher in SRM females as compared to females with normal pregnancy. The prevalence of these antibodies were associated to low subsequent live birth rate whereas the existence of anti H-Y antibodies were related to low male/female ratio in subsequent live births [40]. The male: female ratio for SRM was observed to be 1.49 prior to miscarriages and 0.76 subsequent to miscarriages in a 20 years cohort study [38]. Thus, implicating H-Y antibodies in preventing implantation or successful gestation of male foetus. Considering H-Y antibodies as one of the factors responsible for SRM, IVIG (intravenous immunoglobulin) infusions are commonly used as treatment to neutralize the circulating antibodies, and it has been shown to improve the birth rates in patients with SRM [38].
The rhesus (Rh) blood group system comprises of more than 50 independent antigens and is highly polymorphic of the human blood group [43]. Following ABO, Rh blood grouping system is clinically important in transfusion medicine. The common Rh antigens are D, C or c, and E or e. Of which the D-antigen is greatly immunogenic and stimulates an immune response in 80% of person negative for D-antigen, when transfused with a D-antigen positive blood [44, 45]. Thus, D-antigen typing is routinely performed on every blood donor and transfusion recipient in order to avoid clinical complications due to mismatched transfusions. On the contrary, even with the use of anti-D immunoglobulin prophylaxis, there is still occurrence of D-alloimmunization in pregnancy.
D-alloimmunization (Rh alloimmunization) in pregnancy occurs due to incompatibility of D-antigen between the mother and the foetus. Generally, an individual is categorized as Rh-positive if they show an expression of Rh D-antigen on the erythrocytes, and Rh negative if there is no expression of D-antigen on the erythrocyte surface [46]. The Rh alloimmunization becomes clinically substantial when an Rh negative mother carries a foetus which is Rh-positive. The incompatibility of Rh antigen leads to sensitization of mother to the D-antigen, and also to the production of anti-D antibodies, which can adhere to and possibly lead to destruction of Rh-positive erythrocytes of foetus. Nevertheless, the Rh incompatibility typically does not have an adverse consequence on the initial pregnancy as the foetus is delivered prior to the development of anti-D alloimmune response [47]. Although, it may also occur during the initial pregnancy due to spontaneous antenatal mixing of the foetal and maternal blood. In some instances such as miscarriage, abortion, trauma, childbirth and invasive prenatal diagnosis viz. chorionic villous sampling, amniocentesis, and pregnancy related uterine curettage may lead to feto-maternal haemorrhage thereby causing maternal exposure to foetal blood and consequently leading to alloimmunization [48]. The risk of Rh D immunization is estimated to be 1.5–2% in sensitized women following spontaneous miscarriage and 4–5% after dilation and curettage [49, 50]. Once the mother has been alloimmunized, subsequent pregnancies are at an increased risk, for the development of haemolytic disease of the new born (HDN) if the foetus is incompatible i.e., Rh-positive [45]. The diagnostic and clinical management of HDN is described in Section 4.1.
Alloantibodies against the Rh antigen are the most common reason for intensive haemolytic disease in the neonates. Although the rate at which clinically significant HDFN occurs is relatively low viz. 3/100,000–80/100,000 live births [51]. In comparison to Rh antigen, alloantibodies to Kell (K and k), Duffy (Fya), Kidd (Jka and Jkb), and MNSs (M, N, S, and s) antigens, are also known to lead severe haemolytic disease in the foetus [52]. Although over 50 different non-ABO red cell surface antigens are thought to be involved in leading to HDFN, but the most relevant and significant alloantibodies causing HDFN are anti-RhD [44], anti-Rhc, and anti-Kell (K1) [53]. HDN due to Kell alloimmunization results in haemolysis and direct inhibition of erythropoiesis by Kell antibodies, as the Kell antigen is expressed on the surface of erythroid progenitor [6, 54]. Alloimmunization due to anti-Kell antibodies results in critical foetal disease even at lower maternal antibody titre than in Rhesus disease [6]. ABO incompatibility also causes HDN, but it occurs exclusively in mother with type-O blood with foetus having type-A or type-B blood. 1% of the type-O mothers possess a high titre of IgG antibodies against both A and B antigens. They cross the placental barrier and lead to haemolysis. Mothers with type-A or type-B antigen have the occurrence of IgM antibodies which are incapable of crossing the placental barrier thus have no role in alloimmunization during pregnancy [6].
A neonate delivered by an alloimmunized mother displays clinical indication based on the severity of the disease. General indications are jaundice, pallor, hepatosplenomegaly, and foetal hydrops in severe cases. Neonates with HDN very frequently suffer anaemia due to destruction of RBCs by reticuloendothelial system and in some due to intravascular destruction. Rarely conjugated hyperbilirubinemia is suffered by the neonate due to placental or hepatic dysfunction with severe haemolytic disease.
Foetal anaemia can be diagnosed using ultrasound, cardiotocography and cordocentesis [48]. High resolution ultrasonography has supported in early diagnosis of early hydrops and has also lowered the foetal trauma and fatality rate to approximately 2% while performing percutaneous umbilical blood sampling (PUBS) and placental trauma during amniocentesis. Rh and ABO alloimmunization can be diagnosed using indirect Coombs test and direct antibody test [6]. Currently in order to prevent alloimmunization in mothers having maternal and foetal Rh incompatibility Rh immunoglobulin (RhIG) is administered at the 28th week of pregnancy. This has critically helped in reducing the instances of HDFN due to anti-D alloantibody [6, 55]. Postnatal HDFN treatment consists of intensive phototherapy and exchange transfusions to treat severe hyperbilirubinemia and top-up transfusions to treat early and late anaemia [56].
Maternal alloantibodies against foetal human platelet antigens (HPA) cause FNAIT. It is comparatively an infrequent condition occurring in 1–800/2000 live new born. The alloantibodies are IgG antibodies against the paternal HPA antigens and are responsible for destruction of platelets in the foetus or the newborn. Almost 80% of the instances of FNAIT are a consequence of maternal and foetal incompatibility to HPA-1a, the rest 20% results from incompatibility to HPA-5b on GPIa and other HPAs [57]. In addition to HPA antigens, antibodies against CD36 glycoprotein a member of class B scavenger receptor family [58] is also implicated in the causal of FNAIT. A case study reported, maternal deficiency in expression of CD36 protein lead to maternal immunization against CD36 protein (anti-NAK) [59]. The clinical impact of NAIT is related with maternal immunization against CD36 is analogous to that observed in infants affected by HPA specific antibodies [60].
Alloantibody production by maternal immune system requires the presentation of antigen to maternal T-cell through HLA class II molecules. It was reported that HPA-1a alloimmunization is mediated by interaction of HPA-1a peptides to HLA DRB3*01:01 molecule [57, 61]. This may be a consequence of feto-maternal haemorrhage, which can happen during delivery or abortion, as a consequence of platelet leakage into maternal circulation [62]. Maternal IgG alloantibody thus formed is progressively transported to the foetus through the neonatal Fc receptor, whereas the IgA and IgM are not transported as there are no specific receptors for them. Once through the placenta, the maternal alloantibody opsonises the foetal platelets thereby resulting in their destruction and leading to thrombocytopenia [62, 63, 64].
The clinical indication of FNAIT differs from asymptomatic thrombocytopenia to life threatening intracranial haemorrhage (ICH) [57]. Intraparenchymal haemorrhage in the temporal lobe is also most often noticed in FNAIT [65]. Studies have also shown that antibodies against HPA-1a antigen or thrombocytopenia may also result in decreased birth weight and a very low weight for gestational age which presents a health risk later in life [66]. In many of the FNAIT instance, the illness presents as, petechiae, hematomas, haemoptysis, retinal bleeding and haematuria [57, 67]. Occasionally, the bleeding due to FNAIT is diagnosed during foetal life in ultrasound abnormalities [68]. Without routine screening for HPA antibodies the disease is mostly detected after the delivery of the first affected child. Thus, making antenatal treatment and diagnosis possible only for subsequent pregnancies in order to prevent recurrence of severe FNAIT [69]. FNAIT may be diagnosed using antibody detection methods using serological or ELISA based techniques or by platelet typing using PCR-based assays.
The immediate treatment for thrombocytopenia in case of severe bleeding is platelet transfusion [68, 70]. In addition to transfusion intravenous immunoglobulin IVIG can be provided to prolong the survival of incompatible platelets and reduce the overall impact of thrombocytopenia [71, 72]. The most favourable antenatal treatment in order to prevent bleeding complications in pregnancies with FNAIT is non-invasive IVIG treatment on weekly basis [68]. In FNAIT resulting due to anti-CD36 glycoprotein intrauterine transfusions with compatible RBC and CD36 null platelets are useful in preventing the hazardous clinical effect of the disease [73].
Neonatal alloimmune neutropenia (NAN) is a very rare disorder, but is a life threatening disorder of the neonates. The occurrence of NAN has been estimated to be 1 in 1000/6000 live births. NAN occurs due to maternal sensitization to incompatible paternal foetal granulocyte antigens. The maternal alloantibodies formed against the foetal granulocytes are transported through the placenta which thereby causes the destruction of foetal granulocytes [74].
Maternal alloantibodies against granulocyte-specific antigens HNA-1a and HNA-1b have been accounted widely to cause NAN. Antibodies to Fc gamma RIIb (CD16) and HNA-2a granulocyte antigen are infrequently involved in neonatal neutropenia, if mother is HNA-1 null phenotype [74, 75]. A case study has also reported the involvement of HNA-4b as a causative of severe NAN [76].
Neutropenia in neonates is a self-limiting disorder and lasts for only few weeks, but in some instances, it can prevail for as long as 6 months. In the course of this period, neonates are at severe risk of acquiring infection [75]. Symptomatic neonate suffering NAN frequently present with retarded umbilical cord separation, skin infections, otitis media, or pneumonia within 15 days of life. Most of the infections that occur are mild, but it may at times turn severe. The fatality rate because of NAN has been noted to be around 5%. The severity of NAN is dependent on concentration and the subclass of IgG present [74].
The immune neutropenia correlates with granulocytes specific antibodies present in the serum and can be diagnosed [75] using the granulocyte agglutination test (GAT), the granulocyte immunofluorescence test (GIFT), the monoclonal antibody immobilization of granulocyte antigens assay (MAIGA), an assay called as extracted granulocyte immunofluorescence assay (EGIFA) measures the anti-HNA-1a, -1b, and/or -2 antibodies in the sera. The use of EGIFA assay has been reported to improve the diagnosis and clinical management of patient suspected to have NAN [77]. The treatment for NAN is still a matter of discussion, but the options used for the management of NAN include antibiotics, intravenous immunoglobulin (IVIG), corticosteroids, and human granulocyte colony-stimulating factor (rhG-CSF) [78].
Table 1 summarizes the implication of HLA antigens in complications related to pregnancy. Though it is now well identified that the HLA plays major role in pregnancy, placentation and immune modulation to maintain an immune-tolerance state. This in turn results in foetus being well accepted by the maternal immune system. Alloimmunization and other pregnancy complications result due to maladapted immune system when the maternal immune system is unable to maintain an immune tolerance state towards the foetus.
Disease/disorder | Associated HLA allele/class | Study findings/outcomes | Reference |
---|---|---|---|
Rh isoimmunization | HLA A3, B17, CW2 and DR4. | Inheritance of HLA HLA A3, B17, Cw2 and DR4 increased the risk of Rh immunization. | Kumar et al. [79] |
NAIT | HLA-DRB3*0101. | Presence of HLA-DRB3*0101 restricted CD4+ cells specific for HPA-1a antigen in alloimmunized women. Implicates strong association of DRB3*0101 in immunization of pregnant women against foetal HPA-1a antigen. | Ahlen et al. [61] |
Reduced birth weight of foetus with NAIT | Maternal anti-HLA class I antibodies. | Increased level of maternal anti-HLA class I antibodies in thrombocytopenic neonates are associated with reduce foetal growth. | Dahl et al. [80] |
Reproductive failure (recurrent miscarriages and pre-eclampsia) | Group 2 HLA-C alleles (C2). | Foetus expresses both maternally and paternally inherited HLA-C antigens. Substantial increase in the risk for reproductive disorders with mother possessing KIR “AA” genotype and foetus expressing more C2 copies than mother. | Hiby et al. [35] |
Recurrent spontaneous abortion | HLA-G with 14 bp polymorphism and SNP 3127(C/G) in the 3′UTR. | Substantial increased frequencies of the genotypes with 14 bp polymorphism and the SNP3127 (C/G) in the 3′UTR in RSA women of Caucasian origin. | Larsen et al. [81] |
Recurrent pregnancy loss (RPL) | −1573T > C and −1746C > A SNPs in the promoter of the HLA-G gene HLA-G promoter region haplotype H1(ATCCAGGTAC GCAA) H2(CTTCGAGAAC GCAG). | SNP −1573T > C and −1746C > A in the promoter region of HLA-G gene are associated with RPL H1 is associated with a decreased and H2 is associated with an increased risk of RPL. | Yazdani et al. [29] |
Pre-eclampsia | HLA-G with 14 bp polymorphism. | Increased frequencies of the +14 insertion/deletion HLA-G genotype of offspring were associated with severe and early onset of pre-eclampsia in Chinese population. | Zhang et al. [82] |
Secondary recurrent miscarriage | HY (male specific minor histocompatibility antigen). | Aberrant maternal immune response against foetal HY antigen play a role in secondary recurrent miscarriage and other pregnancy complications. | Christiansen et al. [40] |
Still birth | HY-restricting HLA class II alleles. | Maternal carriage of HY-restricting HLA class II alleles decreases long-term chance of live birth in women with RPL after a boy. | Kolte et al. [41] |
Role of HLA in pregnancy disease/disorders.
The authors declare no conflict of interest.
In the refurbishment of old buildings, especially in the area of monuments [1, 2], capillary building materials, for example, consisting of brick masonry are found very often. Since the building materials of old buildings are often capillary-active materials [3, 4, 5], there is distinctive water absorption and release as well as water transport behaviour on this material. This process is called capillarity. Investigating the capillarity of old building materials can be of considerable relevance. The water absorption and release behaviour is, for example, crucially important for moisture transport and the moisture penetration of components.
The possibilities that result from examining the capillarity of a material in the Environmental Scanning Electron Microscope (ESEM) are explained in this abstract, using a subsequent sealing with injection agents on capillary masonry.
In many cases when renovating old buildings [6], sealing has to be carried out later because no sealing was installed when the object was built or the sealing is no longer adequately functional now. The proof of capillarity and the description of the moisture behaviour of the building materials play a major role here.
A good example is the construction of a subsequent cross-section sealing with injection agents. Although already known from antiquity, the regular use of functioning building waterproofing at capillary building materials began around 1890. Nevertheless, there were no uniform rules for the execution of structural waterproofing at that time. Only in the 1930s, structural waterproofing was normatively regulated. Although the cross-section sealing in massive walls had already a higher priority than other seals on buildings at the end of the nineteenth century, cross-section seals were regularly installed in masonry walls since 1930 onwards. In the old building area, there are very often buildings to find that have a cellar, even if the space requirements made this cellar unnecessary. This is related to the previous construction use, in which the basement was due to lack of sealing technology while permanently moist, but served as a ‘buffer’ to the upper floors, which thereby could be kept sufficiently dry. In this way, the buildings were built without a cross-sectional sealing. For these reasons, solid brick walls in cellars are often encountered in old building renovation and monument preservation, in which there is rising masonry moisture due to non-existent cross-sectional sealing. However, due to usage or conversion requirements of a value retention, there is a great need to permanently seal capillary masonry walls against increasing moisture in the wall cross section in the refurbishment in the renovation of historical monuments. A main group in the retrofitting of masonry cross-section seals is the masonry injection methods, which do not require static interventions [7, 8].
There are currently about 150 different injection agents [7] available for the subsequent cross-sectional sealing of capillary masonry. All injection agents have in common that they are applied by the production of borehole chains in the masonry. The injection agents react chemically. The sealant layer in the masonry is physically formed. There are pressurized and non-pressurized processes to apply the injection medium into the masonry.
However, all injection agents work in the same way: they change the capillarity of the building material and thus also the water transport properties of the material [9]. Therefore, the capillarity of a capillary-active substance that is changed by the injection agent can be used as a reference for the investigations in the Scanning Electron Microscope (SEM) in the ESEM mode. The investigations with the SEM in the ESEM mode can provide information about the efficiency of such a subsequent sealing by means of injection. In order to be able to monitor the injection procedure and to be able to demonstrate the effectiveness of the injection medium, it is therefore necessary to monitor the quality and quantity of the actually changed capillarity on the object [10].
The detection method presented here is based on the contact angle method in the Environmental Scanning Electron Microscope, ESEM. The ESEM is a modified version of a Scanning Electron Microscope, SEM [11, 12]. In contrast to the SEM, the ESEM can be used in low-vacuum mode. This circumstance allows the supply of a medium (here water steam) during the investigation. A cooling table in the chamber allows the sample to be refrigerated while the air in the chamber is at 100% relative humidity. Changing the chamber pressure causes condensation in the ESEM chamber [13]. During the investigation in the ESEM, condensation water droplets are formed on the sample. The contact angles can be determined on the formed drops of water [14]. When measuring the contact angle, one makes use of the interfacial tension of the water. Both static contact angles and dynamic contact angles can be measured in the ESEM. The contact angles provide information about the changed capillarity of the sample material on which the drops were formed. The contact angle can be measured directly in the ESEM or afterwards. The data obtained from this show a geometrically differentiated picture of the changed capillarity of the examined material. The method can provide information about the quality of the injection as well as about the geometric penetration with the injection agent.
The Environmental Scanning Electron Microscope (ESEM) is a special variant of the Scanning Electron Microscope (SEM). The main difference to a conventional Scanning Electron Microscope lies in the lower vacuum in the measuring chamber [15]. Moreover, a special detector is installed for the operation of the ESEM. Due to the lower vacuum (low vac mode), a medium can be supplied to the chamber in ESEM mode. For the examination of building materials, the supplied medium is usually water/water vapour. The gas pressure in the chamber of the ESEM is usually 130–1.300 pascals. In the same way as when using the SEM, the sample is scanned by a focused electron beam in the ESEM. The signal resulting from an interaction with the sample is picked up by the detector and used to generate the image. The ESEM uses the generation of low-energy secondary electrons (0–50 eV), which are emitted from the sample surface as slow electrons. For signal amplification, the ESEM uses the gas in the sample chamber, which generates an amplification cascade through ionization. This system also neutralizes charges on the samples. The most important difference between the ESEM and operation in high vacuum (= SEM) is that in low vacuum the water is not ‘expelled’ from the sample and condensation processes (droplet formation) and can thus be made visible. For this purpose, the detector of the ESEM is not sensitive to light or temperature. In order to be able to visualize the water wetting and drying processes in the ESEM, different aggregate states of the medium, here water, which are pressure- and temperature-dependent, are used.
For this purpose, a cooling table connected to a recirculating cooler is arranged in the chamber of the ESEM. The sample is glued to this cooling table with carbon or conductive silver to ensure optimal temperature conductivity. As part of the investigations in the ESEM, the temperature conditions of the cooling table are fixed while the chamber pressure is changed. This causes a change in the state of aggregation of the medium in the chamber (from gaseous to liquid). If the dew point is reached on the sample, the water condenses out on the sample surface. This process is recorded with the help of pictures. In the ESEM, the forming contact angle of a drop can be measured in situ using the contact angle measurement method. Progressive, receding or static contact angles can be measured on ripe droplets. If a drying process is to be shown, the condensation water that has formed can be evaporated by reducing the chamber pressure, and the drying process is made visible. Technically, the ESEM is very well suited to show dynamic condensation in situ [16, 17, 18, 19, 20] (Figure 1).
Phase diagram of water, P. Körber.
The figure above shows the limit curves of the three phases: gaseous (water vapour), liquid (water) and solid (water-ice). These phase areas meet at the triple point. At this point, the three phases are in thermodynamic equilibrium. The formation of condensation is related to the dependence of the state of aggregation of the phases on temperature and pressure.
Due to the change in the pressure conditions in the ESEM, the dew point inevitably occurs during the investigation in the ESEM, and the water that is gaseous in the medium becomes liquid in the form of droplets on the sample surface (Figures 2 and 3).
Cooling table with circulation cooler, P. Körber.
ESEM chamber: Cooling table with circulation cooler, P. Körber.
The contact angle θ is the angle between the liquid surface and the outline of the contact surface at an interface between a liquid and a solid. The external stress of a liquid is defined by the imbalance of molecules within the liquid and at the liquid boundary (interface between liquid and gas). This intermolecular force that contacts the surface is called surface tension. A drop is formed due to the surface tension of a liquid. In addition, external influences such as gravity play a role shaping the drop. The contact angle of a drop occurs at the contact surface of the drop on a solid and also depends on the shape of the drop. The contact angle can provide information about the wettability of a solid with a liquid. The contact angle of a drop of water placed on a component surface can be measured macroscopically or microscopically. Water is well suited for carrying out a contact angle measurement, as it is characterized by a relatively high surface tension (=0.072 n/m). The principle of the contact angle measurement is illustrated in the Figure 4. The static contact angle is measured by applying a tangent to the point where the water droplet touches the solid surface and the ambient phase (here it is air). The contact angle decreases with increasing wettability of the solid (building material surface). The contact angle θ is defined as an angle at the phase boundary of the gaseous, liquid and solid phases of liquids on a solid surface surrounded by gas [21, 22]. This relationship was already defined in 1805 by Thomas Young.
Contact angle measurement with the tangent method, P. Körber.
Eq. (1): Interfacial tension between solid and gaseous:
In Young’s equation, the solid-gas interfacial tension is calculated by adding the solid-liquid interfacial tension to the liquid-gas interfacial tension and multiplying it by the contact angle. The equation below is used to calculate the Young’s contact angle.
Eq. (2): Young’s equation for calculating the contact angle:
Surface and interfacial tension defines the ‘work’ required to increase the interface area. Within the liquid, the molecules interact in all directions (cohesion), while at the interface there is no interaction of the liquid molecules with the outside (adhesion). Young’s equation describes the balance of these forces. This is viewed at the three-phase contact line and exists when the contact line is balanced and at rest. Then the horizontal forces acting on the contact line exactly cancel each other out. The interfacial tension is temperature-dependent, so the contact angles also depend on the temperature and, for most substances, decrease with increasing temperature. However, because there are other forces acting on the contact line in addition to surface tension, the Young’s contact angle cannot be measured per se. If there are movements of the contact line, one speaks of ‘dynamic contact angles’. When the drop volume increases, one speaks of ‘advancing contact angles’, while when liquids evaporate, one speaks of ‘receding contact angles’. In this context, it can be assumed that the advancing contact angle is always greater than the receding contact angle. The difference between these two contact angles is called ‘contact angle hysteresis’.
The hydrophilic or hydrophobic properties of substances can be precisely determined using the ‘Drop Shape Analysis System’. In this method, a droplet illuminated from behind is observed with a camera and displayed on a monitor. With this method a static contact angle is measured by assuming, for the sake of simplicity, that static conditions are present for the contact angle measurement. In fact, this is not the case, because contact angles determined in this way are also subject to certain, very small, changes during the measurement. However, this inaccuracy is included in the tolerance to be estimated and can therefore remain irrelevant for the purposes considered here.
The static contact angle can be measured using the tangent method, as shown above. The results of the contact angle measurements on building materials are differentiated using the 90° limit in A) hydrophobic > 90° and B) hydrophilic < 90°. In addition to this 90° angle definition, the angle measurements also provide information about the gradual water absorption capacity of the substance being examined. If a dynamic condensation/evaporation process is present, static contact angles can only be measured when the dynamic equilibrium between condensation and evaporation is reached. The contact angle method described here for determining the capillarity of a building material can also be applied macroscopically. In the present case, however, this method is applied microscopically in the ESEM. A reliable optical method for drop shape measurement can be carried out on the drops measured in the ESEM: The Drop Shape Analysis (DSA).
In the Drop Shape Analysis (DSA), images are taken of the droplets that are formed and then examined by using computer software. The contact angle is determined by the use of an image. The software can sharpen the captured image and recognize the contour of the drop. The measurement is computer-aided utilizing a geometric model. In the next step, the surface tension can be calculated applying the ‘Young-Laplace-Fit’ if the density difference and thus the imaging scale between the droplet phase and the surrounding phase are known. Accuracies of ±0.2° can be achieved here.
The optically measured drop contour can be calculated using a conic section equation =>Conic Section Method. The conic section method is based on the assumption that the contour of the drop to be measured describes an arc of an ellipse.
The term ‘hydrophobe’ (hydrophobic) is borrowed from ancient Greek (hẏdor = water and phob = repellent). Hydrophobic describes a water-repellent property of a substance. This means that the substance does not dissolve in water and cannot be wetted by water. The term ‘hydrophil’ (hydrophilic) is also borrowed from the ancient Greek (hẏdor = water and phílos = loving). Hydrophilic means that a substance is water-friendly, water-loving. Hydrophilic describes a water-accepting property of a substance. This means that the substance can be dissolved in water and wetted with water (Figures 5–7).
Contact angle measurement: superhydrophobic, P. Körber.
Contact angle measurement: hydrophobic, P. Körber.
Contact angle measurement: hydrophilic, P. Körber.
The examination method described here for building materials in the ESEM can be used in particular for the question in the hydrophobicity of the substance to be examined. During the investigation in the ESEM, condensation processes are carried out, which provide information on how water-absorbent the examined substance is [23].
The procedure for examining building materials in the ESEM is explained below on the basis of a subsequent waterproofing of capillary building materials using injection agents. Such an injection method is used in particular in historic buildings made of solid building materials and in renovations [9].
Investigations in the ESEM are particularly useful when the question arises to what extent a building material is capillary-active or to what extent the capillarity of the building material has changed. Such changes are conceivable, for example, through the use of injection agents in building waterproofing. In the case of injection agent seals, for example, on brick masonry, the penetration of the injection agent changes the capillarity of the building material in such a way that the transfer of water in the building material is impeded or prevented. In this way, it is possible to subsequently create a cross-section seal in masonry walls. For such a procedure, it is necessary to prove the changed capillarity of the building material. This proof documents the sealing success. In this respect, the condensation in the ESEM is predestined to provide evidence for the use of injection agents for the subsequent sealing. The advantage of the examination method in the ESEM is that very small sample quantities can be evaluated in a very short time. The ESEM investigations on building materials are therefore qualitative, microscopic (imaging) detection methods. In addition to these microscopic methods, there are also macroscopic detection methods to investigate the changed capillarity in building materials [24, 25, 26, 27, 28, 29].
The qualitative microscopic (imaging) detection method in the ESEM as described here can also be used by verifying the macroscopic, also qualitative, detection methods. It can provide comprehensive information about the changes in the capillary building material under the influence of the injection agent used.
Furthermore, the extent to which an injection material was used at all and to which the building material now exhibits hydrophobic properties after use can be verified. With the exact measurements, the hydrophobicity of the building material can be gradually verified. A comparative examination of the building material before and after injection is possible. With the qualitative microscopic (imaging) detection method, as with the macroscopic investigations, local samples are taken from the injection level using mini core drillings and are analysed in the laboratory in the ESEM.
Essentially, significantly less material has to be removed from the structure for the verification method described here.
To examine the building material in the ESEM, samples are to be taken from the injection level. In addition, reference samples of the masonry without adding the injection agent are required.
The reference samples and the samples from the injection level are subjected to condensation in the ESEM. In the ESEM mode, condensation on a microscopic scale can be brought about within the pores of the building material (bricks and mortar). The condensation process is recorded using pictures and, if necessary, using film. During the condensation process, there is a time window in which the contact angle of the forming water droplets can be measured. The measurement of the contact angle can be carried out directly in the ESEM.
In addition, the measurement can also be carried out retrospectively on the images generated in the ESEM. The measured contact angles can be used to determine whether the substance is hydrophobic or hydrophilic. The examination results consist of an imaging procedure that can be evaluated afterwards. In particular, comparisons with the reference samples are possible.
The qualitative microscopic, imaging detection method described here can be flanked and verified by macroscopic examinations. The macroscopic investigations can serve as a calibration function for the ESEM measurements. In this way, serial tests can be carried out, in which differentiated proof of the sealing success of the subsequent building sealing with injection agents can be provided [29].
In Figure 8a–f, shown below, it becomes clear how the condensation water droplets form in the ESEM. After the time window for the formation of the drops has expired, these attract each other and then merge into one another, so that the time window for the measurement is over. The maximum achievable contact angle is relevant for the measurement.
Condensation process on a brick sample in the ESEM, P. Körber.
The following figures show examples of the formation of condensation water droplets in the ESEM on brick and mortar samples (Figures 9–11). Figure 12 shows the contact angle measurement, which takes place directly in the ESEM.
Condensation process on a brick sample in the ESEM, P. Körber.
Condensation process on a mortar sample in the ESEM, P. Körber.
Condensation process on a brick sample in the ESEM, P. Körber.
Measurement of the contact angle in the ESEM, P. Körber.
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\n\n2. SUBMIT YOUR MANUSCRIPT
\n\nAfter approval, you will proceed in submitting your full-length manuscript. 50-130 pages for compacts, 130-500 for Monographs & Edited Books.Your full-length manuscript must follow IntechOpen's Author Guidelines and comply with our publishing rules. Once the manuscript is submitted, but before it is forwarded for peer review, it will be screened for plagiarism.
\n\n3. PEER REVIEW RESULTS
\n\nExternal reviewers will evaluate your manuscript and provide you with their feedback. You may be asked to revise your draft, or parts of your draft, provide additional information and make any other necessary changes according to their comments and suggestions.
\n\n4. ACCEPTANCE AND PRICE QUOTE
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They are known as hydrous phyllosilicate having silica, alumina and water with variable amount of inorganic ions like Mg2+, Na+, Ca2+ which are found either in interlayer space or on the planetary surface. Clay minerals are described by presence of two-dimensional sheets, tetrahedral (SiO4) and octahedral (Al2O3). There are different clay minerals which are categorized based on presence of tetrahedral and octahedral layer in their structure like kaolinite (1:1 of tetrahedral and octahedral layers), smectite group of clay minerals (2:1 of tetrahedral and octahedral layers) and chlorite (2:1:1 of tetrahedral, octahedral and octahedral layers). The particle size of clay minerals is <2microns which can be present in form of plastic in presence of water and solidified when dried. The small size and their distinctive crystal structure make clay minerals very special with their unique properties including high cation exchange capacity, swelling behavior, specific surface area, adsorption capacity, etc. which are described in this chapter. 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This has compromised the ability of the environment to foster life and render its intrinsic values. Heavy metals are known to be naturally occurring compounds, but anthropogenic activities introduce them in large quantities in different environmental compartments. This leads to the environment’s ability to foster life being reduced as human, animal, and plant health become threatened. This occurs due to bioaccumulation in the food chains as a result of the nondegradable state of the heavy metals. Remediation of heavy metals requires special attention to protect soil quality, air quality, water quality, human health, animal health, and all spheres as a collection. Developed physical and chemical heavy metal remediation technologies are demanding costs which are not feasible, time-consuming, and release additional waste to the environment. This chapter summarises the problems related to heavy metal pollution and various remediation technologies. A case study in South Africa mines were also used.",book:{id:"6534",slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Vhahangwele Masindi and Khathutshelo L. Muedi",authors:[{id:"225304",title:"Dr.",name:"Vhahangwele",middleName:null,surname:"Masindi",slug:"vhahangwele-masindi",fullName:"Vhahangwele Masindi"},{id:"241403",title:"M.Sc.",name:"Khathutshelo",middleName:"Lilith",surname:"Muedi",slug:"khathutshelo-muedi",fullName:"Khathutshelo Muedi"}]}],onlineFirstChaptersFilter:{topicId:"14",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83123",title:"Natural Fibers: The Sustainable Alternatives for Textile & Non-Textile Applications",slug:"natural-fibers-the-sustainable-alternatives-for-textile-non-textile-applications",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.106393",abstract:"The increasing environmental concerns and depletion of petroleum resources have increased the importance of natural fibers and have stimulated researchers and industries to use sustainable fibers instead of conventional synthetic fibers. Besides exceptionally brilliant mechanical and physical properties are also attractive aspects of natural fibers enabling the utilization of natural fibers in myriad of textile and non-textile applications such as clothing, and reinforced composite products in various industries such as automotive, building, and furniture. Natural fiber composites are composite materials comprising of reinforcing fibers derived from renewable and carbon dioxide neutral resources such as wood or plants. NFCs find application in molded articles that demand moderate strength for acceptable performance for various indoor and outdoor applications. A rapid drift from oil-derived polymers and mineral-reinforced materials to sustainable alternatives has fostered automotive and packaging industries to start utilizing natural fiber composites in their designs. Accordingly, natural fiber composites are serving as energy efficient and sustainable alternatives replacing traditional materials such as metals, polymeric resins, and reinforcement fibers. A worldwide clamor for green products and thus upsurge in sustainable alternatives have been witnessed as a result of diminishing petroleum reserves worldwide, exorbitant prices of petroleum, and high disposal costs of petroleum-based composites along with inability of decomposition of some petroleum-based composites. Contrastingly, natural materials outshine the petroleum-based products in being renewable, inexpensive, biodegradable, and eco-friendly.",book:{id:"11122",title:"Natural Fiber",coverURL:"https://cdn.intechopen.com/books/images_new/11122.jpg"},signatures:"Yamini Jhanji Dhir"},{id:"82948",title:"Study on Miniaturization of Antenna Using Metamaterials",slug:"study-on-miniaturization-of-antenna-using-metamaterials",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.106222",abstract:"Metamaterials (MTMs) are artificially built materials intended to give its properties from the internal structure, rather than the chemical composition found in natural materials. Electric permittivity (ε) and magnetic permeability (μ) are the two basic parameters which describe the electromagnetic property of a material or medium. Permittivity describes how a material is affected when it is placed in electric field. And permeability describes how a material is affected in presence of magnetic field. Metamaterials may have either negative permittivity or permeability or both may be negative simultaneously. The concept of metamaterials has additionally been utilized to design different kinds of patches with upgraded performance, such as improved gain and enhanced efficiency. Also, it has been utilized for the scaling down of patches. Two parameters are utilized in the collected works for antennas using metamaterials. We can adjust the refractive index of the metamaterial to positive, near-zero or negative values. Utilization of epsilon negative, MNG (μ - Mu negative) or DNG (double negative) are called metamaterial- based antennas and the use of metamaterial unit cell for example complementary split ring resonator, split ring resonator and so on are alluded as metamaterial inspired antennas. The design of complementary split ring resonator and its equivalent circuit will be discussed in this work. CSRR (complementary split ring resonator) provides both isolation enhancement and miniaturization for MIMO antenna.",book:{id:"11824",title:"Metamaterials - History, Current State, Applications, and Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11824.jpg"},signatures:"Andrews Christina Josephine Malathi"},{id:"83080",title:"Boron Doping in Next-Generation Materials for Semiconductor Device",slug:"boron-doping-in-next-generation-materials-for-semiconductor-device",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.106450",abstract:"The article surveys the most recent achievements starting with the boron doping mechanism, mainly focused on doping in semiconductor materials such as Si, Ge, graphene, carbon nanotube, or other 2D materials. Frequently used doping methodologies are discussed, including ion implantation and solid-phase doping, mainly focused on recent developing techniques of monolayer doping. These doped materials’ structural, electronic, and chemical properties are addressed to understand the boron doping effect better. Theoretical and experimental information and data are used to support such atomic-level effects. Therefore, this review can provide valuable suggestions and guidelines for materials’ properties manipulation by boron doping for further research exploration.",book:{id:"11762",title:"Characteristics and Applications of Boron",coverURL:"https://cdn.intechopen.com/books/images_new/11762.jpg"},signatures:"Linh Chi T. Cao, Luqman Hakim and Shu-Han Hsu"},{id:"83055",title:"Boron Clusters in Biomedical Applications: A Theoretical Viewpoint",slug:"boron-clusters-in-biomedical-applications-a-theoretical-viewpoint",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.106215",abstract:"In this chapter, we presented an analysis of the recent advances in the applications of boron clusters in biomedical fields such as the development of biosensors and drug delivery systems on the basis of quantum chemical calculations. Biosensors play an essential role in many sectors, e.g., law enforcement agencies for sensing illicit drugs, medical communities for detecting overdosed medications from human and animal bodies, etc. The drug delivery systems have theoretically been proposed for many years and subsequently implemented by experiments to deliver the drug to the targeted sites by reducing the harmful side effects significantly. Boron clusters form a rich and colorful family of atomic clusters due to their unconventional structures and bonding phenomena. Boron clusters and their complexes have various biological activities such as the drug delivery, imaging for diagnosis, treatment of cancer, and probe of protein-biomolecular interactions. For all of these reactivities, the interaction mechanisms and the corresponding energetics between biomaterials and boron clusters are of essential importance as a basic step in the understanding, and thereby design of relevant materials. During the past few years, attempts have been made to probe the nature of these interactions using quantum chemical calculations mainly with density functional theory (DFT) methods. This chapter provides a summary of the theoretical viewpoint on this issue.",book:{id:"11762",title:"Characteristics and Applications of Boron",coverURL:"https://cdn.intechopen.com/books/images_new/11762.jpg"},signatures:"Ehsan Shakerzadeh, Elham Tahmasebi, Long Van Duong and Minh Tho Nguyen"},{id:"83048",title:"Structural, Magnetic, and Magnetodielectric Properties of Bi-Based Modified Ceramic Composites",slug:"structural-magnetic-and-magnetodielectric-properties-of-bi-based-modified-ceramic-composites",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.106569",abstract:"In this chapter, we introduce a promising composite material, which can be used as a potential candidate in the field of charge storage, sensors, and spintronic devices. The structural, magnetic, and magnetodielectric properties of the pure cum composite samples are investigated. The Rietveld refinement of the X-ray data confirmed the presence of a single (A21am) and mixed phases (A21am + R-3c + Pbam) in the pure and composite sample, correspondingly. The SEM microstructure suggests the contrasting nature of the homogeneous and heterogeneous distribution of grains in the corresponding pure and composite sample. The magnetic properties of the composite sample increase due to the enhanced exchange interaction between the different magnetic ions. The frequency-dependent dielectric subjected to a constant magnetic field indicates the signature of magnetodielectric (MD) coupling for both the samples. The field variation of the MD loop shows the symmetric hysteresis loop in the composite due to the addition of magnetostrictive La0.67Sr0.33MnO3 and the non-collinear antiferromagnetic Bi2Fe4O9 phase. The maximum value of MD% (~0.12%) is enhanced by ~13 times in the composite than in the pure sample. Therefore, the improved MD coupling and symmetric switching of the MD loop of the composite make it a suitable candidate for low power consumption storage devices.",book:{id:"11117",title:"Smart and Advanced Ceramic Materials and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11117.jpg"},signatures:"Rasmita Jena, Kouru Chandrakanta and Anil Kumar Singh"},{id:"83035",title:"Breaking the Property Trade-Offs by Using Entropic Conceptions",slug:"breaking-the-property-trade-offs-by-using-entropic-conceptions",totalDownloads:18,totalDimensionsCites:0,doi:"10.5772/intechopen.106532",abstract:"Entropic conception has been used as an effective strategy for developing materials to break the property recordings of current materials, for example, breaking the trade-off between the high-strength and low-ductility structural alloys. The performance of materials usually under a complex circumstance, a balance of multiple properties, for example, combined the high-strength, high ductility, high conductivity, high corrosion resistance, high irradiation resistance, etc., the strategy of high-entropy-alloy (HEA) will provide a materials design and development technology to realize the goal. Magnetic materials usually exhibit excellent magnetic properties but weak mechanical properties and corrosion resistance. The reported unique behaviors of HEAs, for example, self-healing effects may be the mechanism for the high irradiation resistance of the HEAs, and self-sharpening behaviors of the tungsten-based HEAs main closely be related to the serration behaviors.",book:{id:"11468",title:"High Entropy Materials - Microstructures and Properties",coverURL:"https://cdn.intechopen.com/books/images_new/11468.jpg"},signatures:"Yong Zhang and Xuehui Yan"}],onlineFirstChaptersTotal:83},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:333,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:11,numberOfPublishedChapters:144,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:126,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:13,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",isOpenForSubmission:!0,editor:{id:"205604",title:"Dr.",name:"Tomas",middleName:null,surname:"Jarzembowski",slug:"tomas-jarzembowski",fullName:"Tomas Jarzembowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKriQAG/Profile_Picture_2022-06-16T11:01:31.jpg",biography:"Tomasz Jarzembowski was born in 1968 in Gdansk, Poland. He obtained his Ph.D. degree in 2000 from the Medical University of Gdańsk (UG). After specialization in clinical microbiology in 2003, he started studying biofilm formation and antibiotic resistance at the single-cell level. In 2015, he obtained his D.Sc. degree. His later study in cooperation with experts in nephrology and immunology resulted in the designation of the new diagnostic method of UTI, patented in 2017. He is currently working at the Department of Microbiology, Medical University of Gdańsk (GUMed), Poland. Since many years, he is a member of steering committee of Gdańsk branch of Polish Society of Microbiologists, a member of ESCMID. 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His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. 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He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. 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He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. 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He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. 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He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. 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With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. 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He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. 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He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"87",type:"subseries",title:"Economics",keywords:"Globalization, Economic Integration, Growth and Development, International Trade, Environmental Development, Developed Countries, Developing Countries, Technical Innovation, Knowledge Management, Political Economy Analysis, Banking and Financial Markets",scope:"\r\n\tThe topic on Economics is designed to disseminate knowledge around broad global economic issues. Original submissions will be accepted in English for applied and theoretical articles, case studies and reviews about the specific challenges and opportunities faced by the economies and markets around the world. The authors are encouraged to apply rigorous economic analysis with significant policy implications for developed and developing countries. Examples of subjects of interest will include, but are not limited to globalization, economic integration, growth and development, international trade, environmental development, country specific comparative analysis, technical innovation and knowledge management, political economy analysis, and banking and financial markets.
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He has advised, among others, the United Nations Development Program, Inter-American Development Bank, Organization of American States, Pre-investment Organization of Latin America and the Caribbean, Technical Cooperation of the Suisse Government, and the World Bank. Dr. Ortiz is the author, co-author, or editor of books, book chapters, textbooks, research monographs and technical reports, and refereed journal articles. He is listed in Who’s Who in the World, Who’s Who in America, Who’s Who in Finance and Business, Who’s Who in Business Higher Education, Who’s Who in American Education, and Who’s Who Directory of Economists. Dr. Ortiz has been a Fulbright Scholar and an MSI Leadership Fellow with the W.K. Kellogg Foundation. 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